Clinton's comments added to a growing outcry over Trump's remarks on Tuesday at a North Carolina rally, which some interpreted as a call for violence against his White House rival. His remarks also fueled widespread concerns about his ability to stay on track.

"Words matter, my friends," the former U.S. secretary of state, who rarely engages in direct back-and-forths with her Republican rival, said at a rally in Des Moines, Iowa. "And if you are running to be president or you are president of the United States, words can have tremendous consequences."

"Yesterday, we witnessed the latest in a long line of casual comments from Donald Trump that crossed the line," she said, citing "his casual inciting of violence."

A new Reuters/Ipsos poll taken Aug. 5-8 - before Trump's latest controversy - showed that nearly one-fifth of 396 registered Republicans said they want Trump to drop out of the race.

Trump insisted in an interview with Fox News that his remarks were a call for political, not physical, action.

“There is tremendous political power to save the Second Amendment, tremendous," the New York businessman said. "And you look at the power they have in terms of votes and that’s what I was referring to, obviously that’s what I was referring to, and everybody knows it."

The U.S. Constitution's Second Amendment guarantees a right to keep and bear arms.

"I can’t think of anything remotely comparable to it. No one tells a joke about the opponent getting shot. I’ve never heard it," said Bob Shrum, a top aide for Al Gore's presidential campaign in 2000 and John Kerry's in 2004.

Republicans shaken

High-profile Republicans and rank-and-file voters appeared shaken on Wednesday after a string of Trump misfires, struggling with how to best reject his divisive candidacy. Some pledged to withhold their endorsement and others backed Clinton.

Some, including MSNBC host Joe Scarborough, a former Republican congressman from Florida, called for party leaders to replace Trump on the ticket.

A new Reuters/Ipsos poll taken Aug. 5-8 - before Trump's latest controversy - showed that nearly one-fifth of 396 registered Republicans said they want Trump to drop out of the race and another 10 percent said they "don't know" whether the Republican nominee should or not.

Clinton's campaign, seeing an opening, has moved to bring disenchanted Republicans into the fold by announcing an official intraparty outreach effort on behalf of the Democratic nominee.

Clinton's campaign now has a website for Republicans and political independents to sign up to pledge their support, listing 50 prominent Republicans and independents who have endorsed her.

On Monday, 50 Republican national security officials signed an open letter questioning Trump's temperament, calling him reckless and unqualified to be president.

Other top Republicans, including Senator Susan Collins of Maine this week, have disavowed Trump but said they cannot back Clinton.

James Rohrscheib, 74, a registered Republican and retired U.S. Navy officer from Washington state, told Reuters the reality is the Nov. 8 election will be a "tough one."

"I’m in a quandary as to who I am going to vote for," Rohrscheib said.

Trump has dismissed the defections and criticism as an unsurprising reaction of the so-called Washington elite to his drive to change the status quo.

One group that appears unswayed is Trump's donors. Reuters interviewed nine major Trump donors on Wednesday, and not one said his Second Amendment comment had given them pause.

Trump Texas fundraising co-chair Gaylord Hughey called the interpretation of his remark as condoning violence "ridiculous" and "ludicrous."

"It’s just another issue the press has really twisted to make headlines," Hughey said.

But Mike Smith, a Republican voter and Reuters/Ipsos poll respondent, said the support Trump is still receiving from Republicans "almost seems obligatory rather than voluntary."

"I’m almost at the point where I think I’m going to vote for Hillary. I don't like her," said Smith, a 74-year-old retiree who lives in Clearwater, Florida. "But Mr. Trump is making me very nervous."

Reset abandoned

Republican strategist and Trump supporter Ford O’Connell said Trump has "dug himself a deep hole" with voters and to win the election he will need to "make it a referendum on Hillary Clinton and the 'rigged system.'"

Democratic presidential nominee Hillary Clinton reacts as she arrives at a field office for Representative Debbie Wasserman Schultz in Davie, Florida, August 9, 2016.

Trump sought to do just that by using an economic policy speech in Detroit on Monday to correct a series of missteps that included a prolonged clash with the parents of a fallen Muslim American soldier. But his remarks Tuesday undermined that effort.

"If she gets to pick her judges, nothing you can do folks," Trump said at the rally in North Carolina. "Although the Second Amendment people, maybe there is, I don’t know," he continued.

A federal official familiar with the matter denied a media report that the U.S. Secret Service, which investigates threats against presidents and candidates, had formally spoken with the Trump campaign about his remark.

Trump's comment and the resulting backlash occurred as Reuters/Ipsos polling showed some 44 percent of 1,162 registered voters believe Trump should exit the race, and that as of Tuesday, Clinton led Trump by more than 7 percentage points, up from a 3-point lead late last week.

Strategists and Trump detractors agreed that it would be difficult, if not impossible, to remove Trump from the Republican ticket.

"It’s wishful thinking to believe the Republicans are going to replace its nominee after the convention. People are grasping at straws," Ron Bonjean, a Republican strategist unaffiliated with Trump, told Reuters.

A more likely scenario would be a replay of the 1996 presidential race, when the Republican Party essentially deserted nominee Bob Dole, who was badly trailing President Bill Clinton, to focus on congressional races.